11-111783896-CTATAT-C

Variant names:

• chr11-111783896-CTATAT-C
• rs3833761
• NM_024740.2:c.*2496_*2500delATATA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024740.2(ALG9):​c.*2496_*2500delATATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5296 hom., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: ALG9 NM_024740.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28
• Publications: 1 publications found

Genes affected

ALG9 (HGNC:15672): (ALG9 alpha-1,2-mannosyltransferase) This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ALG9 Gene-Disease associations (from GenCC):

• ALG9-associated autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• ALG9-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• Gillessen-Kaesbach-Nishimura syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-111783896-CTATAT-C is Benign according to our data. Variant chr11-111783896-CTATAT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 302379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024740.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG9	NM_024740.2	MANE Select	c.*2496_*2500delATATA		3_prime_UTR	Exon 15 of 15	NP_079016.2	Q9H6U8-3
	ALG9	NM_001441203.1		c.*2156_*2160delATATA		3_prime_UTR	Exon 16 of 16	NP_001428132.1
	ALG9	NM_001352417.1		c.*2156_*2160delATATA		3_prime_UTR	Exon 16 of 16	NP_001339346.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG9	ENST00000616540.5	TSL:1 MANE Select	c.*2496_*2500delATATA		3_prime_UTR	Exon 15 of 15	ENSP00000482437.1	Q9H6U8-3
	ALG9	ENST00000532425.6	TSL:3	c.*2156_*2160delATATA		3_prime_UTR	Exon 6 of 6	ENSP00000432442.2	H0YCW6

Frequencies

GnomAD3 genomes AF: 0.262 AC: 38960 AN: 148562 Hom.: 5297 Cov.: 19

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 38965 AN: 148666 Hom.: 5296 Cov.: 19 AF XY: 0.262 AC XY: 18965 AN XY: 72348

African (AFR) AF: 0.215 AC: 8640 AN: 40168

American (AMR) AF: 0.340 AC: 5066 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1186 AN: 3460

East Asian (EAS) AF: 0.178 AC: 907 AN: 5102

South Asian (SAS) AF: 0.247 AC: 1166 AN: 4718

European-Finnish (FIN) AF: 0.242 AC: 2330 AN: 9614

Middle Eastern (MID) AF: 0.294 AC: 84 AN: 286

European-Non Finnish (NFE) AF: 0.279 AC: 18825 AN: 67464

Other (OTH) AF: 0.297 AC: 608 AN: 2050

Alfa AF: 0.252 Hom.: 539

Asia WGS AF: 0.211 AC: 729 AN: 3450

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3833761; hg19: chr11-111654620; COSMIC: COSV67645545;